Evaluation of muscle capillary basement membrane in inflammatory myopathy. A morphometric ultrastructural study.

The capillary basement membranes from 16 skeletal muscle biopsies from patients with a clinical and histological diagnosis of inflammatory myopathy and from six controls were analysed ultrastructurally and morphometrically. Resin sections from 244 endomysial capillaries were examined by light microscope, and the results were correlated with findings seen in electron micrographs of these capillaries. The ultrastructural morphometric measurements and the statistical analysis showed that the capillary basement membrane was thick and multilaminated in 87% specimens affected by inflammatory myopathy. No thick or multilaminated basement membrane was observed in controls. In inflammatory myopathy the endomysial space next to the capillaries contained an increased amount of collagen fibrils and showed signs of a chronic reparative process. It is suggested that the thick multilaminated basement membrane in inflammatory myopathy represents an advanced stage of vascular regeneration.

Muscle involvement in Walker-Warburg syndrome. Clinicopathologic features of four cases.

Walker-Warburg syndrome is a lethal autosomal recessive disorder characterized by anomalies of the central nervous system and the eye. Recently, elevation of muscle enzymes and congenital muscular dystrophy have been found to contribute to the diagnosis of this syndrome. The authors studied two pairs of siblings with Walker-Warburg syndrome, offspring of consanguineous parents from two unrelated families. The patients had hydrocephalus, congenital glaucoma, elevated muscle enzymes, and hypotonicity. The histologic and ultrastructural muscular changes were consistent with congenital muscular dystrophy.

Congenital muscular dystrophy with neurological abnormalities: association with Hirschsprung disease.

We report on a baby girl with congenital muscular dystrophy (CMD) with neurological abnormalities ("CMD Plus" condition), who also had Hirschsprung disease. This association may indicate a category of congenital muscular dystrophy with involvement of the visceral nervous system. We propose that Hirschsprung disease be added to the list of anomalies pertaining to the "CMD Plus" array, and that CMD should be considered when Hirschsprung disease occurs with central nervous system anomalies.

Connective tissue of the orbital cavity in retinal detachment: an ultrastructural study.

The connective tissue from Tenon's capsule of 7 patients who underwent surgery for retinal detachment was studied ultrastructurally. Five patients were 58-70 years old, and 2 were young adults. The Tenon capsules of 6 children and of 2 aged patients without retinal problems were used as controls. In young controls the Tenon capsule was composed mainly of round, smooth collagen fibrils and a few elastic fibers. The collagen fibrils varied in size from 70 to 110 nm. In the aged patients with retinal detachment, the collagen fibrils showed marked variation of size and also abnormalities of shape in 4 out of 5 cases. The diameter of collagen fibrils varied from 32 to 160 nm, and the elastic fibers were fewer as compared with controls. The possibility arises that age-related structural changes of the orbital connective tissue could predispose to retinal detachment.

Cerebro-oculo-facio-skeletal syndrome: further delineation.

We report on a newborn infant with cerebro-oculo-facio-skeletal (COFS) syndrome. Congenital muscular dystrophy-like changes were present in this patient. It is debated whether the clinical spectrum of the COFS phenotype should be expanded to include congenital muscular dystrophy:

Massive fibrosis of extraocular muscles related to intraocular tumor.

A resin histological and ultrastructural study of 9 fibrotic extraocular muscles from 2 patients who underwent enucleation because of advanced intraocular malignant melanoma is reported. Total fibrosis of the extraocular muscles was evident in one case and extensive fibrosis in the other case. The patients did not suffer from congenital fibrosis syndrome. Ultrastructurally, the muscle tissue was replaced by collagen fibrils showing great variability of caliber.

End-stage fibrosis of the lateral rectus muscle in myopia with esotropia. An ultrastructural study.

The fibrotic lateral rectus muscle and the medial rectus muscle of 4 patients with esotropia and myopia who underwent surgical correction were studied ultrastructurally. All patients revealed underactivity of the lateral rectus muscle. In 3 patients the underactive lateral rectus was completely fibrotic; in 1 patient there was 80% fibrosis, and the rest of the muscle showed different stages of degeneration. The fibrotic lateral recti were composed of collagen fibrils and remnants of degenerated organelles. The collagen fibrils of the lateral recti were of different sizes, and the mean diameter varied from 65 to 92 nm. On the other hand, the interstitial collagen fibrils of nonfibrotic medial rectus muscles of these patients and also of control muscles showed less variation in size, and the mean diameter was smaller as compared with the fibrotic lateral rectus. It is suggested that the collagen fibrils that compose the fibrotic lateral rectus muscle probably develop under conditions which differ from the normal development of collagen fibrils.

In vivo detection of retroviral particles in mice with hybridoma induced ascites.

Ascites induced by hybridoma cells following their injection into pristane-primed peritoneal cavities of BALB/c mice is often associated with the formation of intra-abdominal tumors related to the transplanted cells. These tumors and adjacent abdominal and extra-abdominal organs were excised and examined by electron microscopy. Clusters of viral particles were seen in nearly all cells composing the hybridoma tumors. The viral particles were usually present in rough ER cisternae of the transplanted tumor cells and at times were observed budding from the cisternal membranes. Individual viral units were doughnut shaped, 80-85 nm in diameter, with two concentric shells of which the outer one was more electron dense. No exogenous viral particles were detected in the peritoneally growing hybridoma cells. All non-tumor tissues examined such as liver, spleen, lung, brain and circulating WBC were free of virus. These findings provide further evidence of viral contamination of hybridomas and demonstrate the mode of persistence of such contamination when cells are placed in-vivo.

Collagen fibril abnormalities in the extraocular muscles in Ehlers-Danlos syndrome.

The dermal collagen fibrils and the fibrils of the extraocular muscles and the conjunctivas of both eyes of a child afflicted with Ehlers-Danlos syndrome (EDS) were studied ultrastructurally. The results were evaluated statistically. Biopsy material was used in all instances. The collagen fibrils from all involved tissues showed a high percentage of size variation. Abnormalities of shape were noted. In the reticular dermis, 48% of fibrils were of normal diameter, 23% were enlarged, and 29% were thinner than normal. In the extraocular muscles, 77% were of normal size, 14.5% were larger, and 8.5% were smaller. In the conjunctivas, 73% of fibrils were normal-sized, 22% were enlarged, and 5% were of small diameter. No small-sized fibrils were encountered in control extraocular muscles.

Severe myalgia in familial Mediterranean fever: clinical and ultrastructural aspects.

Severe myalgia is an uncommon feature of familial Mediterranean fever (FMF). A patient is presented in whom acute myalgia and high fever were the sole clinical findings during an FMF attack. The ultrastructural picture of the muscle tissue during the acute stage was characterised by a large deposition of collagen fibrils. The myalgia subsided during colchicine treatment. The clinical and ultrastructural features of myalgia in FMF are discussed in the light of the relevant literature.

Abnormalities of intramuscular nerves in old mice: an ultrastructural study.

Intramuscular branches of tibial nerves of 5- and 27-month-old mice were compared. Seventeen intramuscular nerve fascicles were studied in each group: 174 myelinated axons were evaluated in the young mice, and 136 in the aged mice. The old mice showed significant decreases in numbers of myelinated axons per nerve, and these had significant decreases in concentrations of mitochondria. Interaxonal collagen and numbers of collagen fibrils were increased, as was the concentration of unmyelinated axons. Myelinated axons of old mice demonstrated myelin disorganization, myelin nodules, degeneration of axoplasm and Schwann cells.

Ultrastructure of the myocardium in dogs with induced jaundice.

Morphological aspects of the myocardium in dogs with experimentally induced jaundice were assessed ultrastructurally. Obstructive jaundice was produced by chronic bile-duct ligation and by choledochocaval anastomosis. The left ventricular myocardium and the papillary muscle were used. Statistical analysis of sarcomere length and of mitochondrial density showed no significant differences between jaundiced and sham-operated dogs. Qualitative evaluation of the mitochondria, the intercalated disc and other sarcoplasmic constituents revealed no damage to the jaundiced dogs.

Comparative ultrastructural study of generalized and localized granuloma annulare.

The dermal changes in four cases of generalized granuloma annulare (GGA) and in four of localized granuloma annulare (LGA) were studied ultrastructurally, and the findings in the two groups were compared. The basic alterations were similar in both types, and showed varied stages of development. The cellular infiltrate was composed mostly of histiocytes. Cell debris was found in all lesions. The degenerative changes affected the collagen fibers, the elastic fibers, and the cellular infiltrate. Of special interest are the following findings in GGA: First, masses of intercellular fibrin material were seen only in the lesions of GGA. Second, thick and multilayered basal lamina around capillaries was apparently more common in the generalized form. These changes may suggest that a more pronounced immune reaction is responsible for the development of the generalized form of the disease.

Ultrastructure of the immediate, histamine-mediated microvascular response in human skin with urticaria pigmentosa.

The immediate microvascular response in the skin of adults with urticaria pigmentosa after activation of mast cells was examined with the electron microscope. Mast cell degranulation was activated by gently rubbing the cutaneous lesion, and biopsy material was removed 5 to 10 min following stimulation. Aspects of mast cell degranulation were found in all the samples. Several indications of the effects produced by histamine release upon permeability of the small upper dermal venules were evident: (1) Scattered endothelial contraction, which resulted in alternation of contracted and dilated portions of the endothelial wall. Deep nuclear indentations in the contracted endothelial cells occurred in a proportion of 53%. (2) Marked dilation and congestion of some venules. (3) Randomly distributed interendothelial gaps, with platelets or red blood cells traversing the gap. The open junctions of small diameter were numerous, whereas the large gaps were numerically few. (3) The presence of a dense material consistent with plasma protein beneath and external to the vascular basement membrane. Vessels showing aspects similar to those occurring after mild thermal injury were noticed. The possibility exists that several mediators and mechanisms superimpose during the early histamine-mediated phase of the vascular response in urticaria pigmentosa following activation of mast cells.

Evidence of Schwann cell degeneration in the aging mouse motor end-plate region.

An ultrastructural evaluation was made of the changes encountered in the motor endplates of the gastrocnemius muscle of old mice in comparison with young-adult mice. In old, 27-month-old mice, a great variety of changes were recorded. The main abnormalities occurred in the axon terminals, the myoneural junctional folds, and the endomysial space. Loss of synaptic vesicles and mitochondria and vacuolization of axon terminals were common. Shrinkage and degenerative changes of axon terminals were noticed. The end-plate abnormalities were closely associated with an increased amount of collagen tissue, degenerated Schwann cells, and cell debris. Degenerated Schwann cells were not encountered in young-adult mice. In the old group, endplates of normal appearance occurred in the proportion of 40%. The young group had normally structured end-plates in the proportion of 85%. The lesions described are not specific for the aging process.

Capillaries of human overacting extraocular muscles.

The capillaries of overacting inferior oblique muscles from children with strabismus and of dog inferior oblique muscles were ultrastructurally described. Biopsy material was used in all instances. The mean diameter of the capillary lumen was 2.03 microns for the human inferior oblique and 2.76 microns for the dog inferior oblique. Quantitative estimates of capillary basement membrane width were obtained by two different methods of measurement. The capillaries of human and dog inferior oblique muscles were compared with capillaries of human gastrocnemius muscle and of dog quadriceps muscle. The data were statistically evaluated. It was found that the mean basement membrane width of capillaries of overacting inferior oblique muscles is quite similar to that of the dog normal inferior oblique muscles, showing 2,049 A in overacting muscles and 1,976 A in normal muscles. With both methods of measurement, the mean basement membrane width of inferior oblique muscles appeared thicker than the mean basement membrane of capillaries of the leg muscles in man and in dog as well. It is suggested that the thickening of the capillary basement membrane of inferior oblique muscles represents a regional characteristic. Marked variation in the thickness of the basement membrane was encountered in all muscles.

Clofibrate-induced muscular syndrome. Case report with ultrastructural findings and review of the literature.

A 70-year-old man with chronic renal failure was treated with clofibrate, 2.0 g daily for 6 days, and subsequently developed clofibrate-induced muscular syndrome (CMS), i.e., myalgia with severe muscle weakness and tenderness. Elevated muscular enzyme activities were found upon examination of his blood. Electron microscopic studies revealed atrophy of some muscle fibers and massive degenerative changes. The atrophic fibers were associated with damaged neuromuscular junctions. A literature survey of 44 cases with CMS is included.